The primary objective is to evaluate the hypothesis that azaserine is carcinogenic because it induced mutagenic changes in cellular DNA. Azaserine induces pancreatic and renal carcinoma in rats while other tissues are less or un-affected. DNA alkylation, DNA strand breaks or alkaline lability, and DNA repair activity induced by azaserine treatment will be studied and compared in pancreas, liver and kidney to see which, if any, of these changes are associated with carcinogenic activity. Radioactive azaserine will be synthesized for use in alkylation and repair studies. Fluorometric detection of DNA in alkaline sucrose gradients will be the major basis of studies of DNA damage and repair. The chemical mechanism of azaserine-DNA interaction will also be analyzed to see if azaserine acts directly or indirectly through a metabolite or degradation product. Dose response in acute studies will be compared with previously obtained dose response data from long-term animal studies of the carcinogenicity of azaserine.